tbuckley/cabot-search huggingface dataset:
OTHR-09. The prevalence and complex management of MEK inhibitor induced cutaneous side effects
Authors: Ashley Meyer, Andrea Ogle, Margaret Shatara, Evan Cantor, Andrew Cluster, Michele McHugh, Mary Beck, Stephanie Reiners, Carrie Coughlin, Mohamed Abdelbaki, Nicole Brossier
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Cutaneous side effects commonly occur with MEK inhibitor (MEKi) therapy and can be challenging to manage. METHODS: A retrospective chart review was performed on sixteen pediatric patients treated with MEKi therapy for at least three months. These patients were diagnosed with either a brain tumor, plexiform neurofibroma, Langerhans Cell Histiocytosis, or Parkes Weber Syndrome (PWS). OBJECTIVES: To describe cutaneous side effects from MEKi therapy, compare the side effect profiles of patients treated for different diagnoses, and compare the side effect profiles between different MEKi agents. RESULTS: The most prevalent cutaneous toxicities for all eligible patients were acneiform rash (81%, most common), paronychia (50%, second most common), hair changes and xerosis. Mean number of cutaneous skin toxicities were 3.2 (trametinib group: 3.4, selumetinib group: 2.8). Only one patient, treated with trametinib for PWS, did not experience a cutaneous side effect. The average number of interventions (new medication or over-the-counter product) recommended to prevent or treat cutaneous-related toxicities was 6.8 per person, the majority of those were for acne and paronychia. Over 75% of the interventions were topical. Of those who experienced an acneiform rash, the average number of recommended interventions were 3.1. Sixty two percent of these patients developed acne within the first cycle; average time to development was 2.6 months into therapy. Most exhibited improvement overtime following intervention. Those patients who experienced paronychia were treated with a mean of 3.1 interventions – 37.5% developed paronychia within the first cycle of therapy; average time to development was 3.9 months into therapy. CONCLUSIONS: Cutaneous side effects are common, occur early in therapy, and require multiple interventions. The number and complexity of these interventions may further complicate the overall management of cutaneous side effects given that the responsibility of the administration falls on the patient. This differs from traditional chemotherapy regimens.
Effect of transition from inpatient oncology service to oncology consult service on fellow burn out and training.
Authors: Anosha Tariq, Talha Aijaz, Vatsala Katiyar, Adam Rojan
Journal: Journal of Clinical Oncology (2022)

11023 Background: The hematology-oncology inpatient service at the University of Louisville underwent a major change in July 2021 from a medical oncology service run by hematology/oncology fellows and attendings to a hospitalist-run service with hematology/oncology fellows and attendings sharing patient care responsibility as a consulting service. We planned this study because, to date, no published work has studied the effect of transitioning from an inpatient to consult service on fellow burnout, education, and training. Methods: A survey was distributed in July 2021, and a follow-up survey was sent in January 2022. The survey had 38 questions regarding the impact of the workload on time for study, research, personal and professional life, which were scored from 1 to 5. Two tail paired t-test was used to compare the difference in means. The survey also contained questions from the Mayo Clinic Resident Well-Being Index (RSWBI). This index has been validated to identify distress among fellows and allows for the comparison of local results with national data from RSWBI. In RSWBI, scores range from 0-7, with 0 being the lowest risk and 7 being the highest risk of burnout. A cut-off of a score ≥ 5 identifies individuals with a high degree of distress, is associated with an increased risk of error, suicidal ideation, and burnout, and has been validated in more than 1700 residents/fellows. Results: We distributed the survey to 2nd and 3rd-year fellows. 5/6 fellows completed the survey. 3 of them were male and 2 females. Change in inpatient service structure did not impact time for study, research, patient encounter, or ability to handle the volume of work. Improvement in adequate time preparing for clinic was statistically significant (P=0.03), and other improvements were also noted in concentration, time for family, and better personal and professional relationships (Table). RSWBI median score before the transition was 3.6, which improved to 2.0 after the transition to consulting service, which was similar to the national average where the median score was 2.0 among 8237 residents/fellows. 2 fellows (40%) were at high risk of distress before the transition. 1 fellow (20%) was at high risk of distress after the transition, which was comparable to the national average where 19.4% resident/fellows scored ≥5. Conclusions: These results show increased levels of distress in fellows that improved to the national average following transition from a primary inpatient medical oncology service to a consult service.[Table: see text]
Real-world outcomes of patients with human epidermal growth factor 2 (HER2)–positive breast cancer receiving neoadjuvant therapy without adjuvant ado-trastuzumab emtansine (T-DM1).
Authors: Massimo Di Iorio, Mitchell J. Elliott, Jordan L Scott, Abhenil Mittal, Consolacion Molto, Faris Tamimi, David W. Cescon, Eitan Amir, Nicholas Meti
Journal: Journal of Clinical Oncology (2022)

584 Background: HER2-positive early-stage breast cancer (EBC) treated with neoadjuvant chemotherapy and HER2-targeted therapy has favourable outcomes, especially for those attaining pathologic complete response (pCR). Among those with residual invasive disease (RD), outcomes are variable. Replacing adjuvant trastuzumab with ado-trastuzumab emtansine (T-DM1) reduces the risk of recurrence, but increases toxicity and cost. The magnitude of benefit of T-DM1 may be small among patients with RD and favourable prognostic features. Here we report on real-world outcomes of patients with HER2-positive EBC treated with neoadjuvant therapy without adjuvant T-DM1. Methods: We performed a single institution, retrospective review of HER2-positive EBC treated with neoadjuvant chemotherapy and trastuzumab between January 1st, 2012 and February 1, 2021. We excluded patients who received adjuvant T-DM1. We collected clinical and pathologic characteristics, treatment data, and outcomes events. We estimated 3-year disease-free survival (DFS), a validated endpoint in HER2-positive EBC, using Kaplan-Meier with recurrence and/or death as events. Outcomes were reported in subgroups based on known prognostic factors. The study was approved by the University Health Network Research Ethics Board. Results: The study comprised 193 patients with a median follow-up of 30 months. The majority (n=160, 83%) received neoadjuvant anthracycline and taxane-based chemotherapy; 42 (22%) received neoadjuvant pertuzumab. All received adjuvant trastuzumab. Median age was 53 years (range 25-87), 113 (59%) patients had estrogen receptor (ER) positive disease, and 82 (42%) had pCR. In total, 16 events were observed, of which 13 (81%) were distant recurrences (including 5 (31%) in the brain) and 3 (19%) were locoregional. Of these, 14 (88%) occurred in the first 3 years of follow-up. Estimated 3-year DFS was 98.6% in patients with pCR, and 85.4% in patients with RD. Patients with ER positive disease had excellent outcomes, regardless of pathologic nodal (ypN) status. The highest risk of recurrence was in ER negative and ypN positive disease (Table). Conclusions: Real-world outcomes of patients with HER2-positive EBC treated with neoadjuvant therapy without adjuvant T-DM1 are favorable, including those with RD if ER positive. The expected benefit of adjuvant T-DM1 in this group is therefore likely to be small. Patients with ER- disease had poorer outcomes irrespective of nodal status. Further research to identify patients with RD for whom the benefit of T-DM1 is unlikely to merit its added toxicity and cost is warranted. [Table: see text]
Identification of biomarker associated with Trop2 expression in breast cancer: Potential implication for targeted therapy.
Authors: Ning Liao, Jianguo Lai, Yuting Luo, Xiaofang Qi, Cheukfai Li
Journal: Journal of Clinical Oncology (2022)

e15120 Background: Trop2 has been confirmed to enhance tumor proliferation, metastasis and invasion in various epithelial tumors. Breast cancer (BC) patients with high Trop2 protein expression have better prognosis and objective response rates. Thus, this study aimed to explore potential biomarker associated with Trop2 protein expression in BC. Methods: BC patients with complete clinical parameters were enrolled, including age, estrogen receptor (ER) status, progesterone receptor (PR) status, human epithelial growth factor receptor 2 (HER2 status), molecular subtype, Ki67 status, T stage, N stage, TNM stage, PD-L1 and Trop2 protein expression level. Univariate and multivariate ordinal logistic regression analyses were performed to identify the independent factor for Trop2 protein expression level. Immunohistochemical analysis was conducted to detect the protein expression level of Trop2 in BC. Kaplan–Meier analysis and the log-rank test were executed to assess the survival difference between low- and high- gene expression level of Trop2. Results: A total of 65 BC patients from the Guangdong Provincial People’s Hospital were included. Based on the univariate and multivariate ordinal logistic regression analyses, Ki67 status was the only independent factor for Trop2 protein expression level (P &lt; 0.05). This finding revealed that BC patients with higher Ki67 status may harbor higher Trop2 protein expression level. According to cBioPortal database, the mutation rate of Trop2 was 2.1% and mutation type was amplification. BC patients with low Trop2 gene expression level had significantly greater survival prognosis (P &lt; 0.05). Conclusions: We performed the comprehensive analysis of the Trop2 in BC patients. It has the potential to guide individualized targeted treatment in BC patients.
External validation of WGS-based antimicrobial susceptibility prediction tools, KOVER-AMR and ResFinder 4.1, for Escherichia coli clinical isolates
Authors: Tess Verschuuren, Thijs Bosch, Valentina Mascaro, Rob Willems, Jan Kluytmans
Journal: Clinical Microbiology and Infection (2022)

To externally validate whole genome sequence-antimicrobial susceptibility testing phenotype prediction tools KOVER-AMR and ResFinder 4.1 for Escherichia coli clinical isolates from Dutch routine care.A random sample of 234 E. coli and 283 third generation cephalosporin-resistant E. coli isolates from urine and blood were collected (2014-2017). Culture-antimicrobial susceptibility testing was performed using VITEK 2 and BD Phoenix. Sequences were used as input for KOVER-AMR-SCM, KOVER-AMR-CART, and ResFinder 4.1. The concordance, major error rate (MER), and very major error rate (VMER) were calculated, with subsequent comparison to U.S. Food and Drug Administration (FDA) criteria (MER ≤3% and VMER with a 95% confidence interval ≤1.5-≤7.5%).ResFinder 4.1 performed better than KOVER-AMR-models; however, neither tool achieved overall (V)MERs below FDA criteria. KOVER-AMR-SCM, KOVER-AMR-CART, and ResFinder 4.1, MER (cumulative all antimicrobials) were: 5.1% (4.4-5.9), 4.3% (3.6-5.0), and 5.1% (4.5-5.8), respectively. MERs ≤3% were achieved for 6 (SCM) and 5 (CART) of the 11 tested antimicrobials for KOVER-AMR-models and for 9/13 antimicrobials tested with ResFinder 4.1. KOVER-AMR-SCM, KOVER-AMR-CART, and ResFinder 4.1 cumulative VMERs were: 26% (24-28), 29% (27-31), and 11% (9.2-12). VMERs with a 95% CI ≤ 1.5-≤7.5 were only achieved for 4/13 tested antimicrobials with ResFinder 4.1.In this study, whole genome sequence-antimicrobial susceptibility testing phenotype prediction tools KOVER-AMR and ResFinder 4.1 did not meet the FDA criteria needed for clinical diagnostic use in 517 E. coli clinical isolates from Dutch routine care. The tested tools should be further improved before they can be used for clinical decision making.
Central nervous system (CNS) outcomes and progression patterns in patients with <i>RET</i> fusion-positive lung cancers treated with selpercatinib.
Authors: Yonina R. Murciano-Goroff, Christina J. Falcon, Sabrina T. Lin, Aradhika Dhawan, Grace Grimaldi, Dazhi Liu, Clare Wilhelm, Reeja Thomas, Alexia Iasonos, Alexander E. Drilon
Journal: Journal of Clinical Oncology (2022)

3109 Background: Selpercatinib, a potent/selective RET inhibitor, is approved for the treatment of RET fusion-positive non-small cell lung cancers. While the drug is known to have substantial intracranial activity (intracranial ORR 82%) in patients with existing brain metastases, (1) central nervous system (CNS) outcomes in patients without brain metastases and (2) CNS progression patterns in patients with brain metastases have not been explored. Methods: Patients with advanced RET fusion-positive lung cancers were prospectively treated with selpercatinib on the registrational LIBRETTO-001 trial (NCT03157128) or the LIBRETTO-201 multi-center expanded access program (EAP, NCT03906331). Key overall and CNS eligibility criteria were previously presented. Patients with and without pre-selpercatinib brain metastases who underwent serial CNS and extracranial imaging were eligible for analysis. The data cutoff was November 24, 2020. Cumulative incidence rates (CIRs) were calculated using a competing risk model with systemic progression of disease (PD) or death as competing risks; patients with simultaneous CNS and systemic PD were treated as having had CNS PD. Results: Sixty-two patients (48 LIBRETTO-001, 14 EAP) were identified. Median age was 64. Thirty-two (52%) were female and 47 (76%) were never smokers. The most common 5’ fusion partner was KIF5B (68%). The median number of prior therapies was 2 (range 1-11); 34% received prior multikinase inhibitor therapy. The median time on treatment was 21.8 months. Thirty-one (50%) patients had no baseline brain metastases. In these patients, the CIR of CNS metastasis was 0% at 6 months and 12 months; none of these patients developed CNS metastasis during selpercatinib treatment. The 9 patients that progressed did so extracranially. Of the 31 patients with baseline brain metastases, 12 (39%) had prior CNS radiation and 3 (10%) had prior CNS surgery. At the time of data cut-off, 23 patients had some evidence of progression, including 8 in both the CNS and systemically, 6 only in the CNS, and 9 only systemically. Overall, 17 of the 31 patients with baseline brain metastasis did not develop evidence of CNS progression as of the data cut. Among patients with baseline brain metastasis, the CIR for evidence of CNS PD was 6.7% at 6 months and 27.4% at 12 months. Conclusions: In patients with RET fusion-positive lung cancers without baseline brain metastases, new CNS metastases were not observed during selpercatinib therapy. Among patients with baseline brain metastasis, a substantial number did not experience progression in the CNS on treatment.
Empowering colorectal cancer patients and caregivers through clinical trials education in COLONTOWN.
Authors: Steve Schwarze, Julie Clauer, Manju George, Lindsey Musick, Nancy Seybold, Adrian Terek
Journal: Journal of Clinical Oncology (2022)

e24129 Background: Clinical trials are increasingly part of the continuum of care for colorectal cancer patients, particularly those with metastatic disease. Yet most patients have limited knowledge about clinical trials, and many struggle to navigate the myriad barriers to enrollment. To bridge this gap, PALTOWN supports a broad array of activities in its COLONTOWN online community to help patients and caregivers interested in pursuing clinical trials. The function and impact of these activities is examined here. Methods: A comprehensive inventory of all clinical trial-related activity was conducted across three main sources: 1) resources and activity in COLONTOWN’s nine clinical trial-focused groups; 2) clinical trial materials posted in COLONTOWN UNIVERSITY, an online disease education center; and 3) patient feedback on clinical trial programming. Results: The MSS and MSI-High clinical trial groups in COLONTOWN serve more than 2,200 members, and more than 1,000 members are served by mutation- and location-specific trial groups. These groups have helped at least 187 members enroll in a clinical trial between 2019 and 2022. Among 10 trial-related activities, a majority (6/10) focused on sharing biomedical information, including : 1) patient-friendly descriptions of new trials; 2) explanations of trial results; 3) abstracts, articles, and videos from professional outlets such as ASCO Daily Post and OncLive; 4) patient-created resources on clinical trial basics in COLONTOWN UNIVERSITY; 5) “Doc Talks” by prominent CRC oncologists; and 6) patient advocates serving as information liaisons between patients and NCI Task Forces. A smaller number of activities (3/10) focused on psycho-social support from peers, including 1) accounts of patient experiences while seeking and participating in trials; 2) strategy discussions about how and when to pursue trials; and 3) “Alanna Project” database of members on a trial. COLONTOWN’s Clinical Trial Workshop (1/10) offers a novel approach to integrating biomedical education with psycho-social support via a four-week, peer-led clinical trial navigation program. Assessment of the cognitive and behavioral outcomes of the workshop demonstrate improvements in all four dimensions of health literacy: the ability to access, understand, appraise, and apply relevant information in the search for clinical trials. Conclusions: COLONTOWN's clinical trial programming offers comprehensive clinical trial education to patients and caregivers that leads to enrollment in trials. By embedding that education within a supportive community of peers, it enhances patients' capacity to collaborate with health care professionals in making informed decisions about clinical trials.
Association of pathologic response and survival after peri-operative therapy in resected pancreatic adenocarcinoma: KU cancer center experience.
Authors: Brett Rozeboom, Maximillian Martinez, Kathan Mehta, Ameer Hamza, Anusha Chidharla, Anwaar Saeed, Raed Moh'd Taiseer Al-Rajabi, Joaquina Celebre Baranda, Sean Kumer, Timothy Schmitt, Christopher Erik Lominska, Andrew Hoover, David Akhavan, Prasad Dandawate, Shrikant Anant, Subhrajit Saha, Ankita Tiwari, Stefan H. Bossmann, Weijing Sun, Anup Kasi
Journal: Journal of Clinical Oncology (2022)

e16254 Background: Neo-adjuvant therapy (NAT) and associated pathologic complete response (pCR) rates have correlated with improved survival in resected pancreatic ductal adenocarcinoma (PDAC). In this study, we explored the relationship between pathologic response, peri-operative therapy, and survival, especially the impact of change in adjuvant therapy in patients with no/poor path response to NAT. Methods: Retrospectively reviewed 66 PDAC patients who received NAT ± radiation and underwent resection at KU Cancer Center between 2011-2022. We compared DFS and OS between Path Responders vs Non-Responders based on standard Tumor Regression Scores from pathology reports. A subanalysis was performed in path non-responders based on switch in adjuvant therapy (AT) versus not. Results: Patient characteristics are summarized in the table. Among 66 PDAC patients, 50 (75.8%) achieved a path response (G0-G2), 16 (24.2%) experienced no/poor path response (G3). Of the 50 pts who achieved a path response, 4 (8.0%) had a complete path response (pCR; G0), 5 (10%) marked response (G1), 41 (82%) moderate response (G2). Median DFS (mDFS) was 17.3 months (95% CI: 12.7-22.4) in Path Responders vs 15.9m (95% CI: 9.6-35.8) in Non-Responders [p=0.59]. Median OS (mOS) was 32.9m (95% CI: 23.4-41.5) vs 27.7m (95% CI: 15.2-38.2), respectively [p=0.39). A sub-analysis in the Non-Responders (n=16) based on switch in AT (n=8) vs not (n=3), revealed mDFS 16.4m (95% CI: 9.6-41.8) when AT was switched vs mDFS 11.3m (95% CI: 5.9-16.6) when AT was not switched [p=0.24]; and mOS 30.6m (95% CI: 15.7-60.3) vs 17.2 months (95% CI: 6.7-27.7), respectively [p=0.18]. Conclusions: Our study found no statistical difference in DFS and OS between Pathologic Responders and Non-Responders to neo-adjuvant therapy. However, a sub-analysis within Pathologic Non-Responders revealed a longer DFS and OS after switching adjuvant therapy without reaching statistical significance, likely due to small sample size. Our findings warrant validation in a larger cohort as switch in adjuvant therapy could potentially change the treatment landscape for Pathologic Non-Responders.[Table: see text]
Phase Ib/II study of BCL-2 inhibitor lisaftoclax (APG-2575) safety and tolerability when administered alone or combined with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in patients with estrogen receptor-positive (ER<sup>+</sup>) breast cancer or advanced solid tumors.
Authors: Kevin Kalinsky, Anthony W. Tolcher, Shushen Wang, Funda Meric-Bernstam, Robert Winkler, Mingyu Li, Xuemei Sun, Wentao Pan, Bishnuhari Paudyal, ZHIYAN LIANG, Ming Lu, Dajun Yang, Yifan Zhai
Journal: Journal of Clinical Oncology (2022)

TPS1122 Background: Various cancers evade apoptosis by overexpressing BCL-2 proteins. Investigational agent lisaftoclax (APG-2575) is a novel, potent, selective BCL-2 inhibitor, while palbociclib inhibits cyclin-dependent kinases (CDK) 4 and 6. In preclinical studies, palbociclib decreased proliferation of ER + breast cancer cell lines by arresting them in the G1 cycle phase. Preclinical data demonstrate favorable, complementary effects of palbociclib when combined with a BCL-2 inhibitor and support this combination in patients with ER + / human epidermal growth factor receptor 2-negative (HER2 - ) metastatic breast cancer. Methods: This global multicenter open-label dose escalation and dose expansion study is assessing the safety of lisaftoclax monotherapy in patients with histologically or cytologically confirmed advanced solid tumors that have progressed on standard therapy or when combined with CDK4/6 inhibitor palbociclib in physiologically postmenopausal women with ER + / HER2 - metastatic breast cancer that has progressed or relapsed after treatment with a CDK4/6 inhibitor. This trial consists of 2 parts: a phase Ib dose escalation phase using a standard 3+3 design to determine the maximum tolerated dose (MTD) of lisaftoclax as a single agent in patients with solid tumors, as well as both the MTD and recommended phase 2 (RP2D) dose of lisaftoclax when combined with palbociclib in women with ER + / HER2 - metastatic breast cancer. Phase II of this study is a signal-seeking expansion of lisaftoclax at RP2D when combined with palbociclib in women with ER + /HER2 - metastatic breast cancer. This phase is being conducted using Simon’s Minimax two-stage design. The primary objective for phase II is to determine clinical benefit response, and secondary efficacy endpoints include overall response rate, duration of response, time to response, and progression-free survival. Lisaftoclax is being administered orally once daily in a 28-day cycle at the assigned dose. Clinical trial information: NCT04946864.